WO2007019522A2 - Inversion de troubles naissants chez l'adulte avec des facteurs de simulation d'une colonie de granulocytes - Google Patents

Inversion de troubles naissants chez l'adulte avec des facteurs de simulation d'une colonie de granulocytes Download PDF

Info

Publication number
WO2007019522A2
WO2007019522A2 PCT/US2006/030930 US2006030930W WO2007019522A2 WO 2007019522 A2 WO2007019522 A2 WO 2007019522A2 US 2006030930 W US2006030930 W US 2006030930W WO 2007019522 A2 WO2007019522 A2 WO 2007019522A2
Authority
WO
WIPO (PCT)
Prior art keywords
granulocyte
colony stimulating
effective dose
disease
stem cells
Prior art date
Application number
PCT/US2006/030930
Other languages
English (en)
Other versions
WO2007019522A3 (fr
Inventor
Carlos Lopez
James K. Petell
Fred Siegel
Joanne Wojciesek
Original Assignee
Carlos Lopez
Petell James K
Fred Siegel
Joanne Wojciesek
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Carlos Lopez, Petell James K, Fred Siegel, Joanne Wojciesek filed Critical Carlos Lopez
Publication of WO2007019522A2 publication Critical patent/WO2007019522A2/fr
Publication of WO2007019522A3 publication Critical patent/WO2007019522A3/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/193—Colony stimulating factors [CSF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/48—Reproductive organs
    • A61K35/51—Umbilical cord; Umbilical cord blood; Umbilical stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/48—Reproductive organs
    • A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
    • A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis

Definitions

  • a method for treating adult onset neurodegenerative diseases and diabetes by administering an effective dose of Granulocyte-Colony Stimulating Factors.
  • Parkinson's disease is an example of a progressive neurodegenerative disease. It is usually diagnosed in adulthood, usually when the patient is about 55 years of age, and is characterized by tremors, rigidity, and bradykinesia. It is well understood that many of the abnormalities found in these patients are due to the loss of dopamine (DA) neurons in the substantia nigra and the depletion of striatal dopamine levels. More recently, there has been a re-evaluation of the signs and symptoms found in Parkinson's disease patients that has led to the conclusion that Parkinson's disease is a systemic disease with involvement of peripheral nervous tissue. For example, the loss of the sense of smell has been found to be an early sign of Parkinson's disease that is found in most patients.
  • DA dopamine
  • Parkinson's disease a progressive neurodegenerative disease characterized by Parkinson's disease .
  • This symptom of disease is probably due to loss of neurons in the olfactory bulb of the brain.
  • orthostatic hypotension has been shown to be one of the more common signs of Parkinson's disease, probably due to a direct effect on the peripheral nervous system (PNS) of the host.
  • PNS peripheral nervous system
  • Clinical manifestations of Parkinson's disease are not apparent until over 80% of the central or peripheral neurons have degenerated.
  • Most new Parkinson's disease patients are started on dopamine agonists (DA) when first diagnosed, but usually progress to L- DOPA (L-dopamine), the precursor of dopamine in tissue.
  • DA dopamine agonists
  • L-DOPA is used to relieve Parkinsonian motor signs, but has very little effect on PNS signs and symptoms of disease. In fact, its long-term use is usually associated with diminished efficacy and increasingly bothersome side effects.
  • Other examples of chronic degenerative neurological disorders that might be treated in a similar manner include macular degeneration, urinary incontinence, Alzheimer's disease, Multiple Sclerosis and short term memory deficiency. These disorders have in common three characteristics; they are usually diagnosed late in life, there is evidence of familial, but not Mendelian genetic, inheritance of each disease, and patients will have had a period of time as adults before diagnosis of disease when the host appears to function normally without evidence of signs or symptoms of the chronic disease.
  • GDNF Glial-Derived Neurotrophic Factor
  • Granulocyte-Colony Stimulating Factor Treatment of stem cell donors with a five-day course of Granulocyte-Colony Stimulating Factor or its pegalated derivative causes the release of stem cells from the bone marrow into the circulating blood and greatly increases the number of hematopoietic and other stem cells that could be harvested from the donor.
  • This procedure requires Granulocyte-Colony Stimulating Factor be administered to otherwise normal donors in order to release stem cells into the peripheral blood where they can be collected by leukophoresis and prepared for transplantation.
  • Many studies have reported the use of Granulocyte-Colony Stimulating Factor in normal volunteers and normal donors, usually at a dose of 5 to 10 micrograms per kg per day for 4 to 8 days. The most common toxicities were bone pain, headaches, and fever.
  • Granulocyte-Colony Stimulating Factor While the toxicities were frequent, the severity was generally mild and very few normal donors had to discontinue Granulocyte-Colony Stimulating Factor because of the side effects. Persons treated with Granulocyte-Colony Stimulating Factor were found to have a surge in peripheral blood stem cells 4 to 7 days after initial treatment. The use of Granulocyte-Colony Stimulating Factor for mobilizing peripheral blood stem cells is widespread and appears to be safe and to be capable of generating the stem cells needed for allogenic or autologous transplantation.
  • Granulocyte-Colony Stimulating Factor is capable of mobilizing peripheral hematopoietic stem cells
  • Granulocyte-Colony Stimulating Factor could induce the recruitment of either local or migration of peripheral stem cells to injured neural tissue, differentiate and restore neural function required for the slowly developing lesions found in most chronic diseases.
  • a self-repair system has not been described in human studies.
  • Type 1 Diabetes is a major public health problem in the United States affecting 16 million people and accounts for one sixth of all health related expenditures.
  • Type 2 (formerly referred to as noninsulin-dependent diabetes).
  • Type 1 is characterized by beta cell loss and absolute insulin deficiency.
  • Type 2 diabetics Of the patients with diabetes today, approximately 90 to 95% of the inflicted are Type 2 diabetics. It is generally characterized by elevated fasting blood glucose and lack of sensitivity to insulin and impaired insulin secretion.
  • the prevalence of Type 2 diabetes is about 7 percent for persons between 45 to 64 years of age.
  • the microvascular and macrovascular complications of Type 2 diabetes causes significant morbidity and mortality in affected individuals.
  • Diabetic retinopathy, neuropathy, and nephropathy are major causes of functional limitations and disability in this patient population.
  • diabetics may be treated with one, and typically two, of several oral drugs able to lower blood glucose levels which include sulfonylureas, metformin, alpha-glucosidase, troglitazone, and repaglinide.
  • sulfonylureas include sulfonylureas, metformin, alpha-glucosidase, troglitazone, and repaglinide.
  • sulfonylureas include sulfonylureas, metformin, alpha-glucosidase, troglitazone, and repaglinide.
  • these agents act on one of four mechanisms that alter renal function, liver metabolism, insulin secretion or breakdown of complex carbohydrates. If these drugs are insufficient, insulin treatment may be prescribed alone or together with these oral agents.
  • Type 2 diabetes was found to be effectively controlled by periodically administering of Granulocyte-Colony Stimulating Factors offering a new approach and a revolutionary treatment for this disease.
  • Granulocyte-Colony Stimulating Factors offering a new approach and a revolutionary treatment for this disease.
  • the administered patient was provided a long term reversal of disease symptoms allowing a more normal lifestyle, a better efficacy for control, an extended period of control without a daily drug requirement, and the potential for reduced side effects for treatment.
  • the present invention is directed to provide a method of treating symptoms associated with a neurodegenerative disease in a human by administering an effective dose of Granulocyte- Colony Stimulating Factor or its derivatives, Granulocyte-Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof. More preferably, the invention is directed to provide a method for the reversal of symptoms associated with Parkinson's Disease in a human through periodically administering of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof.
  • the invention herein is directed to provide a method of treating symptoms associated with diabetes in humans by administering an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof. More preferably, the invention is directed to provide a method for the extended reduction of blood glucose levels associated with Type 2 diabetes in a human through administering of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof.
  • one or more symptoms of an adult onset neurodegenerative disease are treated by administering to a human an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof.
  • Adult onset neurodegenerative diseases include but are not limited to Parkinson's Disease, macular degeneration, urinary incontinence, age related short term memory loss, and multiple sclerosis.
  • one or more symptoms of adult onset Parkinson's disease are reversed by administering an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof.
  • an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof is administered to a human with an adult onset neurodegenerative disease by subcutaneous injection, transdermal patch, intravenously, orally or other means.
  • a typical period for administering Granulocyte-Colony Stimulating Factors is from about 1 to 8 days, preferably ranging 3 to 6 days.
  • an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof are administered daily to a human for treatment of an adult onset neurodegenerative disease ranging from 0.1 micrograms to 20000 micrograms per kg body weight per day, preferably between 1 to 20 micrograms per kg body weight per day.
  • an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof is administered to a human for treatment of an adult onset neurodegenerative disease for about 1 to 8 days and repeated about every 2 to 18 weeks, and more preferably every 4 to 10 weeks.
  • an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof is administered into a human for the reversal of one or more symptoms associated with Parkinson's Disease.
  • Symptoms of Parkinson's Disease may be either central nervous system or peripheral nervous system derived and, include but are not limited to, orthostatic hypotension, resting tremor, rigidity, postural instability, micrographia, urinary and gastrointestinal incontinence and lack of sense of smell.
  • an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof is administered into a human with an adult onset neurodegenerative disease in combination with stem cells a selected from a group consisting of harvested umbilical cord stem cells, progenitor stem cells or stem cell lines.
  • stem cells a selected from a group consisting of harvested umbilical cord stem cells, progenitor stem cells or stem cell lines.
  • harvested stem cells, progenitor stem cells or stem cell lines are pre-treated with Granulocyte- Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof before injection.
  • the level of blood glucose in an adult onset Type 2 diabetic is reduced by treatment with an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof.
  • the blood glucose levels after treatment remain reduced by 2 days longer, more preferably 1 week or longer and most preferably 4 weeks or longer.
  • an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof is administered into a human for treatment of diabetes, and preferably Type 2 diabetes, by subcutaneous injection, transdermal patch, intravenously, orally or other means.
  • a typical period for administering is from about 1 to 8 days, more preferably ranging 3 to 6 days.
  • an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof administered into a human for treatment of diabetes ranging from 0.1 micrograms to 20000 micrograms per kg body weight per day, preferably between 1 micrograms to 20 micrograms per kg body weight per day.
  • an effective dose of Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or combinations thereof is administered for treatment of Type 2 diabetes for about 1 to 8 days and the treatment is repeated about every 2 to 18 weeks, and preferably every 4 to 10 weeks.
  • Granulocyte-Colony Stimulating Factors is administered at least one weeks before the blood glucose levels rise to levels prior treatment.
  • Granulocyte-Colony Stimulating Factor or its derivatives is effective in improving other brain associated neural diseases that include but are not limited age related memory impairment, Schizophrenia, and Alzheimer's.
  • Gramulocyte-Colony Stimulating Factors means Granulocyte-Colony Stimulating Factor or its derivatives, Granulocyte- Macrophage Colony Stimulating Factor or its derivatives, or other biologically or chemically derived compounds or factors that are functional equivalent.
  • Mainntaining means slowing, interrupting, arresting or stopping the progression of the disease.
  • Reversing means the improvement of one or more symptoms from the diseased state rather than maintaining the current state of disease.
  • Treatment means maintaining the state of the disease or the reversal of a disease symptom.
  • Fig. 1 demonstrates the long term reversal of Parkinson's Disease symptoms using the United Parkinson's Disease Scale to evaluate the condition of the patient administered with Granulocyte-Colony Stimulating Factor over two and one-half years.
  • Fig. 2 demonstrates the reduction of blood glucose levels below the preferred normal limit after Granulocyte-Colony Stimulating Factor was administered to Type 2 diabetic patient.
  • FIG. 3 shows the average time course for blood glucose levels of six treatments with GCSF.
  • the present invention described herein was aimed at performing treatments using Granulocyte-Colony Stimulating Factors administered to patients with neurodegenerative diseases, more preferably Parkinson's disease, to determine whether Granulocyte-Colony Stimulating Factors were able to maintain the state of the diseases, and preferably reverse the symptoms, either partially or completely.
  • neurodegenerative diseases more preferably Parkinson's disease
  • the treatment of the neurodegenerative disease, Parkinson's Disease, with Granulocyte-Colony Stimulating Factors reversed symptoms of both the central nervous system (CNS) and peripheral nervous system (PNS).
  • CNS central nervous system
  • PNS peripheral nervous system
  • Granulocyte-Colony Stimulating Factors delivered in an effective dose was able to reduce blood sugar levels of patients with adult onset Type 2 diabetes for a significant period of time.
  • GCSF Granulocyte-Colony Stimulating Factor
  • human pluripotent granulocyte colony-stimulating factor as well as chemically synthesized polypeptides sharing its biochemical and immunological properties has been previously disclosed (U.S. Pat. Nos. 6,379,661; 6,004,548; 6,830,705; 5,676,941, 6,027,720; 5,994,518; 5,795,968; 5,214,132; 5,218,092; 6,261,550; 4,810,643; 4,810,321).
  • Granulocyte-Colony Stimulating Factor examples include analogs which retained their three-dimensional structures and hybrid molecules maintaining their biological and structural integrity were described by Osslund (U.S. Patent 6,261,550).
  • functional GCSF variants include any proteins, peptides or fragments thereof that are at least 70%, preferably 80% and most preferably at least 90% identity to full-length human GCSF amino acid sequence or its nucleotide sequence.
  • Modifications of GSCF to improve functionality or resident serum clearance include but are not limited to polyethyleneglycol and polyethyleneglycol derivatives thereof, glycosylated forms (LenogastrimTM) (WO 00/44785), norleucine analogs (U.S. Pat. No.
  • GCSF GCSF and albumin fusion protein
  • An increase in biological or functional activity over the native peptide may reduce the amount of dose and / or the time period required for treatment.
  • Any chemical or biological entity that functions similar to GCSF can also be employed.
  • GCSF, or the drug name Filgrastim is currently being sold as Neupogen® and its polyethylene glycol modified or pegulated form, with the drug name Pegfilgrastim, sold as NeulastaTM.
  • GMCSF Granulocyte- Macrophage Colony Stimulating Factor
  • Examples of closely related functional forms include Granulocyte- Macrophage Colony Stimulating Factor (GMCSF) whose coding DNA sequence and protein including amino acid sequence are known as well as various methods employed to produce recombinant proteins (U.S. Pat. No. 5,641,663).
  • Examples of functional GMCSF variants include any proteins, peptides or fragments thereof that are at least 70%, preferably 80% and most preferably at least 90% identity to full-length human GMCSF amino acid sequence or its nucleotide sequence.
  • Modifications of GSCF to improve functionality or resident serum clearance include but are not limited to polyethyleneglycol and polyethyleneglycol derivatives thereof, glycosylated forms, norleucine analogs, addition of amino acids at either terminus to improve folding, stability or targeting, and fusion proteins, such as GCSF and albumin fusion protein (AlbugraninTM).
  • fusion proteins such as GCSF and albumin fusion protein (AlbugraninTM).
  • An increase in biological or functional activity over the native peptide may reduce the amount of dose and / or the time period required for treatment.
  • Any chemical or biological entity that functions similar to GMCSF can also be employed. Examples of GMCSF, or the drug name Sargramostim, which are currently being sold, include Leukine® or Leucomax® and Leucotropin®.
  • AMD3100 or derivatives thereof (U.S. Pub. No. 2002/0058653, 2003/0130250, U.S. Pat. No. 6,670,354) effective in enhancing or elevating the populations of progenitor and/or stem cells may be used in conjunction with GSCF or GMCSF derivatives or combinations thereof. Treatments with compounds may be administered at the same time or prior to administration of GSCF or GMCSF.
  • oral dosages, and methods thereof, of Granulocyte-Colony Stimulating Factor have been described by Nomura and Kazutoshi (U.S. Pat. No. 5,597,562) that allow for dosage reductions, facilitate dose control, and increase the practical usefulness of the bioactive proteins.
  • Brimelow and Nanette U.S. Pat. No. 6,497,689 have described preferred pH ranges comprising sulfate ions for stabilizations.
  • Granulocyte-Colony Stimulating Factors has been suggested to act as a neuroprotective agent in vitro and may be used for the potential treatment of diseases that result from oxidative stress or apoptosis such as in cerebral ischemia and traumatic brain injury (U.S. Pub. No. 2004/0141946; 2006/0153799).
  • the work was focused on an in vitro model using STAT proteins and GCSF receptor or rat model for cerebral ischemia. It was suggested that GCSF may be used to "treat" broadly ischemic or hypoxic related diseases as well as neurological, psychiatric and neurodegenerative diseases as neuroprotective agent acting to slow, interrupt, arrest or stop the progression of the disease.
  • the work fails to provide insights on how treatment would work in humans as no human study was performed.
  • Type 2 diabetes is an example of a non-neurological disorder that appears to be due to the lack of insulin sensitivity of the target cells or insufficient levels of insulin in response to blood glucose. Although it is unknown what causes Type 2 diabetes, it is clear that the disease is usually first diagnosed as an adult and is usually progressive (in terms of the need for therapy to control blood sugar). Type 2 diabetics will have had a relatively long period of time with normal blood sugar before the fasting blood sugar levels begin to rise and the disease can be diagnosed. Other non-neurological disorders include osteoarthritis and benign prostate hypertrophy.
  • Granulocyte-Colony Stimulating Factors are likely to enhance or be required in the treatment of neurodegenerative diseases by stem cell therapy.
  • a method for the differentiation of stem cells in culture using Granulocyte-Colony Stimulating Factor and other factors, including lipopolysaccharides, to obtain immune system suppressor cells and immune systems stimulator cells was described by Ogle et al (U.S. Pat. No. 6,165,785).
  • a method is useful in differentiating stem cells that are destined to become replacements for damaged cells in neurodegenerative disease and diabetes.
  • injected stimulated stem cells into patients with adult onset Type 2 diabetes and adult onset neurodegenerative diseases, such as Parkinson's Disease, are able to initiate repair or to enhance the effect over Granulocyte-Colony Stimulating Factors alone.
  • the patients provided these stem are also administered Granulocyte-Colony Stimulating Factors for further benefit.
  • patients with the adult onset diseases are injected with stem cells that are not pretreated with Granulocyte-Colony Stimulating Factors but subsequent treatment and provided with an effective dose of Granulocyte-Colony Stimulating Factors to enhance response.
  • Example 1 Reversal of Symptoms with Parkinson's Disease with Granulocvte-Colony Stimulating Factor
  • the patient was a 61 year-old male with a six year history of Parkinson's Disease. When first diagnosed two years prior, the patient was started on 100 milligrams Amantidine twice daily and 5 milligrams Selegiline twice daily and on increasing doses of Permax, 25 micrograms to 250 micrograms three times daily.
  • Granulocyte-Colony Stimulating Factor (GCSF) was typical of adult onset Parkinson's disease.
  • the patient had blood work performed 7 days before treatment which included CBC, ESR, urine analysis and chemistry screen.
  • CBC CBC
  • ESR urine analysis and chemistry screen.
  • the male patient approximately 67 kg body weight diagnosed with Parkinson's Disease had history of modest hyperlipidemia which was controlled on medications. Physical exam was normal except for some cogwheeling especially on the right.
  • Granulocyte-Colony Stimulating Factor was started at a daily dose of 330 micrograms (1.1 ml) through injection for 5 consecutive days. Patient experienced slight bone pain on second and third days of therapy.
  • GCSF caused reversal of one or more symptoms of Parkinson's Disease upon treatment with the first dose.
  • the reversed symptoms included orthostatic hypotension, resting tremor, rigidity, postural instability, handwriting and urinary and gastrointestinal incontinence.
  • Example 2 Long Term Treatment of Parkinson's Disease using Granulocvte-Colonv Stimulating Factor.
  • UPDS Unified Parkinson's Disease Scale
  • UPDS evaluates mostly CNS symptoms of Parkinson's Disease
  • four indicators of PNS symptoms were also evaluated included urinary and gastrointestinal incontinence, orthostatic hypotension and loss of smell.
  • the induction of orthostatic hypotension was evaluated by taking blood pressure before and after going from a lying down position to sitting and then standing position and each time taking blood pressure with an automatic apparatus. A drop of 50 mm was associated with developing lightheadedness and orthostatic hypotension. All four indicators were reversed relative to the state prior to GCSF treatment. In fact, the patient was able to exercise without fainting or having to rest (orthostatic hypotension), enjoyed foods and drinks (smell), resolved urinary and gastrointestinal incontinence, and gained sense of smell resulting in a higher quality of life.
  • Example 3 Reduction of Blood Glucose Levels in Type 2 Diabetics Administered with Granulocyte-Colony Stimulating Factor.
  • Example 4 Long Term Controlled Reduction of Blood Glucose Levels in Type 2 Diabetics Administered with Granulocyte-Colony Stimulating Factor.
  • Example 2 To examine the long term effect of Granulocyte-Colony Stimulating Factor on a patient with adult onset Type 2 diabetes, the patient in Example 2 was monitored for approximately two and one-half years for fasting blood glucose almost every morning. Starting with the first day of therapy with GCSF, every 5 day period was averaged and the mean used to compare blood glucose levels.
  • Figure 3 shows the analyzed data from blood sugar determinations around six courses of GCSF. Each time after the GCSF is administered the blood sugar dropped well within the normal range after about twenty to thirty days after the start of therapy, hi one case drug was not administered until late in the period of follow-up and then the nadir was reached about twenty-five days after the start of that course.

Abstract

L'invention concerne une méthode de traitement de diabètes et de maladies neurodégénératives naissantes chez un adulte par administration d'une dose efficace de facteurs de simulation d'une colonie de granulocytes.
PCT/US2006/030930 2005-08-04 2006-08-04 Inversion de troubles naissants chez l'adulte avec des facteurs de simulation d'une colonie de granulocytes WO2007019522A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US70570705P 2005-08-04 2005-08-04
US60/705,707 2005-08-04

Publications (2)

Publication Number Publication Date
WO2007019522A2 true WO2007019522A2 (fr) 2007-02-15
WO2007019522A3 WO2007019522A3 (fr) 2007-11-08

Family

ID=37728005

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2006/030930 WO2007019522A2 (fr) 2005-08-04 2006-08-04 Inversion de troubles naissants chez l'adulte avec des facteurs de simulation d'une colonie de granulocytes

Country Status (2)

Country Link
US (3) US20070031373A1 (fr)
WO (1) WO2007019522A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009102021A1 (fr) * 2008-02-14 2009-08-20 Kyoto University Traitement de maladie rétinienne par activation de la fonction de cellule souche issue de moelle osseuse ou de cellule progénitrice de celle-ci

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008137571A1 (fr) * 2007-05-01 2008-11-13 Florida Atlantic University Procédés de traitement de maladies neurodégénératives
US20120093764A1 (en) * 2010-10-19 2012-04-19 Dipnarine Maharaj Treatment of diabetes using g-csf and hyperbaric oxygen
US8889630B2 (en) * 2011-12-23 2014-11-18 Carlos Lopez Method for hair regrowth using Granulocyte-Colony Stimulating Factor
US10039808B2 (en) 2014-10-22 2018-08-07 Michael Chez Method of treating or improving neurological function in a human subject
US9925244B1 (en) 2015-02-17 2018-03-27 Michael Chez Treatment of warts in non-immunosuppressed patients

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040136998A1 (en) * 2002-10-30 2004-07-15 Bander Neil H. Methods and compositions for treating or preventing insulin-related disorders using binding agents specific for prostate specific membrane antigen
US20040141946A1 (en) * 2002-12-31 2004-07-22 Axaron Bioscience Ag Methods of treating neurological conditions with hematopoietic growth factors

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7361505B1 (en) * 1991-07-08 2008-04-22 Neurospheres Holdings Ltd. Multipotent neural stem cell compositions
JP2002543096A (ja) * 1999-04-26 2002-12-17 ステム セル ファーマシューティカルズ，インコーポレーテッド ＴＧＦ−αポリペプチド、機能性断片およびそれらの利用法
JP2005508141A (ja) * 2001-05-25 2005-03-31 セローノ ジェネティクス インスティテュート ソシエテ アニニム ヒトｃＤＮＡおよびタンパク質、ならびにそれらの使用
US7601688B2 (en) * 2002-06-13 2009-10-13 Biocon Limited Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus
US20040136969A1 (en) * 2002-10-02 2004-07-15 New York University Adult bone marrow derived stem cells
AU2003283004A1 (en) * 2002-10-22 2004-05-13 Waratah Pharmaceuticals, Inc. Treatment of diabetes
JPWO2004091661A1 (ja) * 2003-04-15 2006-07-06 中外製薬株式会社 糖尿病治療剤
CN1589904A (zh) * 2003-09-01 2005-03-09 北京大学 造血干细胞动员剂制备治疗糖尿病药物的用途
CA2540529C (fr) * 2003-10-03 2012-03-13 Vib Vzw Moyens et procedes de recrutement et d'identification de celles souches
TW200526638A (en) * 2003-10-22 2005-08-16 Smithkline Beecham Corp 2-(3,4-dimethylphenyl)-4-{[2-hydroxy-3'-(1H-tetrazol-5-yl)biphenyl-3-yl]-hydrazono}-5-methyl-2,4-dihydropyrazol-3-one choline
WO2006045105A2 (fr) * 2004-10-20 2006-04-27 Vitro Diagnostics, Inc. Generation et differenciation de lignees de cellules souches adultes
US7850960B2 (en) * 2004-12-30 2010-12-14 University Of Washington Methods for regulation of stem cells

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040136998A1 (en) * 2002-10-30 2004-07-15 Bander Neil H. Methods and compositions for treating or preventing insulin-related disorders using binding agents specific for prostate specific membrane antigen
US20040141946A1 (en) * 2002-12-31 2004-07-22 Axaron Bioscience Ag Methods of treating neurological conditions with hematopoietic growth factors

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009102021A1 (fr) * 2008-02-14 2009-08-20 Kyoto University Traitement de maladie rétinienne par activation de la fonction de cellule souche issue de moelle osseuse ou de cellule progénitrice de celle-ci

Also Published As

Publication number Publication date
US20120082642A1 (en) 2012-04-05
US8084421B2 (en) 2011-12-27
US20090170752A1 (en) 2009-07-02
US20070031373A1 (en) 2007-02-08
WO2007019522A3 (fr) 2007-11-08

Similar Documents

Publication Publication Date Title
US20120082642A1 (en) Reversal of Adult Onset Disorders with Granulocyte-Colony Stimulating Factors
Palmour et al. Characterization of a peptide from the serum of psychotic patients
EP1817047B1 (fr) Utilisation de scf et de scf dans le traitement de l'ischemie cerebrale et des troubles neurologiques
EP2881112B1 (fr) Composition pharmaceutique pour promouvoir la restauration d'une lésion nerveuse et son application
JP2004520345A (ja) 糖尿病を有する被験者にガストリン／ｃｃｋ受容体リガンド及びｅｇｆ受容体リガンド組成物を用いた島細胞新生治療方法の効果持続
EA013565B1 (ru) Варианты полипептидов нейбластина, способы их получения и их применение
WO2008137571A1 (fr) Procédés de traitement de maladies neurodégénératives
DE60021360T2 (de) Vegf angiogenische wachstumsfaktoren zur behandlung von peripherer neuropathie
EP0388226B1 (fr) Moyen de traitement de la démence sénile, des troubles de la mémoire et états comparables
EP3609522A2 (fr) Méthodes et composés pour le traitement du diabète
JP4463885B2 (ja) 劇症肝炎疾患治療剤
US20170049677A1 (en) Method for reversing hair loss and the loss of cuticle growth and density by administering effective courses of granulocyte-colony stimulating factor
Klokol et al. Cell therapy as the main stratagem of anti-aging and regenerative medicine
US5830857A (en) Method of treating epilepsy
US8895505B2 (en) Method of treatment of type 2 diabetes
WO2021062371A1 (fr) Traitements à médiation par tnfrsf25 de maladies et de troubles immunitaires
US20220111011A1 (en) Method and Compounds for Treating Diabetes and Associated Metabolic Diseases
US20230120635A1 (en) Peptides and Fragments for Treating Diabetes and Associated Metabolic Diseases
CN109865127B (zh) 经修饰的胸腺素β4在治疗糖尿病周围神经病变方面的用途
WO2009018643A2 (fr) Utilisation d'un composé pharmaceutique contenant crotoxine pour traiter des dystonies musculaires
Czapska et al. Sotagliflozin, an inhibitor of sodium–glucose cotransporters 1 and 2 (SGLT1/2), as a new therapeutic approach for patients with type 1 diabetes mellitus
WO2020223299A1 (fr) Méthodes et compositions pour traiter une lésion du snc
WO2020070540A1 (fr) Méthodes et composés pour le traitement du diabète
be a Major Research News and Notes
KR20060079183A (ko) 다발성 뇌신경계 위축증에서의 인간 성장 호르몬의 용도

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 06800988

Country of ref document: EP

Kind code of ref document: A2